Abstract
We developed an automated 2-tiered Fuhrman’s grading system for clear cell renal cell carcinoma (ccRCC). Whole slide images (WSI) and clinical data were retrieved for 395 The Cancer Genome Atlas (TCGA) ccRCC cases. Pathologist 1 reviewed and selected regions of interests (ROIs). Nuclear segmentation was performed. Quantitative morphological, intensity, and texture features (n = 72) were extracted. Features associated with grade were identified by constructing a Lasso model using data from cases with concordant 2-tiered Fuhrman’s grades between TCGA and Pathologist 1 (training set n = 235; held-out test set n = 42). Discordant cases (n = 118) were additionally reviewed by Pathologist 2. Cox proportional hazard model evaluated the prognostic efficacy of the predicted grades in an extended test set which was created by combining the test set and discordant cases (n = 160). The Lasso model consisted of 26 features and predicted grade with 84.6% sensitivity and 81.3% specificity in the test set. In the extended test set, predicted grade was significantly associated with overall survival after adjusting for age and gender (Hazard Ratio 2.05; 95% CI 1.21–3.47); manual grades were not prognostic. Future work can adapt our computational system to predict WHO/ISUP grades, and validating this system on other ccRCC cohorts.
Highlights
Clear cell renal cell carcinoma is the most common malignant tumor of epithelial origin in the kidney [1]
The Cancer Genome Atlas (TCGA) Clear cell renal cell carcinoma (ccRCC) clinical data, including Fuhrman’s grade, and hematoxylin and eosin (H&E) Whole slide images (WSI) were retrieved for 395 cases [18,19]
Computer extracted morphological features reflected the variation of ccRCC nuclei as observed by pathologists
Summary
Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of epithelial origin in the kidney [1]. Diagnostic challenges can occur with the presence of other morphological features such as sarcomatoid or spindle cell pattern, when higher grade ccRCC show more eosinophilic staining in the cytoplasm, or other renal cancer histologic types (e.g. papillary RCC type and chromophobe RCC) exhibit clear cytoplasm [2,3]. At the time of this work, Drs Lin and Irshad were both employees of BIDMC, and were not at commercial companies (i.e., Foundation Medicine for Lin and Figure-Eight Technologies Inc for Irshad). Those two commercial affiliations did not provide salaries for Lin and Irshad at the time of the study, and did not have any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
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